Melanin is produced by tyrosinase from tyrosine via DOPA in melanocytes, which are pigmentation cells present in the stratum basale in the epidermis, and it has been known that tyrosinase-related protein-1/2 (Trp-1/2), in addition to tyrosinase, is involved in the melanin biosynthesis procedure (Korner and Pawelek, Science (1982) 217:1163-1165; Kobayashi et al., EMBO J (1994) 13:5818-5825; and Yokoyama et al., Biochim Biophys Acta (1994) 1217:317-321), and cyclic AMP (cAMP) and extracellular signal-activated kinases-1/2 (ERK1/2) thereby are continuously involved as upper signals of tyrosinase expression (Marshall, Cell (1995) 80:179-185; and Busca and Ballotti, Pigment Cell (2000) 13:60-69).
Melanocytes are affected by several factors, such as external conditions (e.g., ultraviolet radiation and inflammation) and hormones (e.g., melanin stimulating hormone (MSH) and thyroid stimulating hormone (TSH)).
Melanin absorbs the light energy of ultraviolet light in the sunlight to protect cells that are deep in the skin from damage due to the ultraviolet light, but the abnormal excessive production of melanin causes abnormal skin pigmentation, such as chloasma, freckles, or pigmentation, and on the contrary, the less production of melanin causes hypomelanosis (leukoderma), such as vitiligo, nevus depigmentosus, pseudoleucoderma atopicum, Tinea versicolor, morphea, allergy, post-inflammatory depigmentation, idiopathic guttate hypomelanosis, and piebaldism (Bolognia and Pawelek, J Am Acad Dermatol (1988) 19:217-255; and Pinto and Bolognia, Pediatr Clin North Am (1991) 38:991-1017).
Of the hypomelanosis diseases, vitiligo results from the destruction of melanocytes, and the other diseases result from a reduction in the amount of melanin produced in melanocytes.
For the treatment of the above diseases, there are photochemical methods using light sensitizers such as psoralen, invasive methods such as surgery, and methods inducing skin re-pigmentation through the administration of drugs having melanocyte proliferation activity or melanogenesis promotion activity, such as the ingredients of leadwort root, ginger, pippali, and black pepper (Ancient Science of Life, (1990) Vol. IV, No. 4, 202-206).
Obesity, which is the cause of various diseases, is responsible for 80% of diabetic patients and 21% of heart disease patients, and causes huge social and economical losses. Therefore, the development of safe and effective anti-obesity drugs can reduce the huge social and economical losses. However, the medicines capable of solving market situations are limited to appetite suppressants and fat uptake inhibitors, falling short of expectations, and have various side effects as described below. Xenical (Roche) induced the inhibition of lipase secreted from the pancreas and the digestive system to inhibit fat absorption, accompanied by side effects, such as a low weight loss effect of 2-3% and frequent diarrhea. Reductil (Abbott) suppresses the appetite through the inhibition of serotonin and noradrenaline uptake, leading to a weight loss effect of 5-10%, but has side effects including cardiovascular diseases, such as stroke and myocardial infarction, so Reductil was removed from the market by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) in 2010 through the suspension of use and prescription and the recommendations for voluntary recall, and was taken off the market by Korea Food & Drug Administration on October 2010. Further, a large number of products that have been developed as an anti-obesity drugs have so far been prohibited from being sold due to severe side effects thereof. For example, aminophylline has been reported to have broad side effects throughout the mental nervous system, circulatory system, and digestive system in spite of its excellent effect of reducing body fat. Also, fenfluramine, dexfenfluramine, topiramate, ephedrine, etc. have been banned from being marketed as obesity drugs.
Throughout the entire specification, many papers and patent documents are referenced and their citations are represented. The disclosure of the cited papers and patent documents are entirely incorporated by reference into the present specification and the level of the technical field within which the present invention falls, and the details of the present invention are explained more clearly.